The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

García-Suástegui, Wendy Argelia; Ramos-Chávez, Lucio Antonio; Rubio-Osornio, Moisés; Calvillo-Velasco, Minerva; Atzin-Méndez, J A; Guevara, Jorge; Silva-Adaya, Daniela

doi:10.1155/2017/4680732

Cited by 79 publications

(48 citation statements)

References 144 publications

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“…Pyrethroids are metabolised by oxidation mediated by cytochrome P450 (CYP450) enzymes (37). In the brain, it is CYP2E1 that acts against environmental chemicals and plays a vital role in neuronal detoxification (68,69). However, its overexpression in the brain tissue, as reported by Galal et al after deltamethrin treatment (25), could increase the risk of neurotoxicity.…”

Section: Inflammationmentioning

confidence: 98%

Pyrethroid exposure and neurotoxicity: a mechanistic approach

Mohammadi

Ghassemi-Barghi

Malakshah

et al. 2019

Archives of Industrial Hygiene and Toxicology

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Pyrethroids are a class of synthetic insecticides that are used widely in and around households to control the pest. Concerns about exposure to this group of pesticides are now mainly related to their neurotoxicity and nigrostriatal dopaminergic neurodegeneration seen in Parkinson’s disease. The main neurotoxic mechanisms include oxidative stress, inflammation, neuronal cell loss, and mitochondrial dysfunction. The main neurodegeneration targets are ion channels. However, other receptors, enzymes, and several signalling pathways can also participate in disorders induced by pyrethroids. The aim of this review is to elucidate the main mechanisms involved in neurotoxicity caused by pyrethroids deltamethrin, permethrin, and cypermethrin. We also review common targets and pathways of Parkinson’s disease therapy, including Nrf2, Nurr1, and PPARγ, and how they are affected by exposure to pyrethroids. We conclude with possibilities to be addressed by future research of novel methods of protection against neurological disorders caused by pesticides that may also find their use in the management/treatment of Parkinson’s disease.

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Section: Inflammationmentioning

confidence: 98%

Pyrethroid exposure and neurotoxicity: a mechanistic approach

Mohammadi

Ghassemi-Barghi

Malakshah

et al. 2019

Archives of Industrial Hygiene and Toxicology

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“…NAV2 localizes in the nucleus and cytoplasm and may play a role in processes of cellular outgrowth and migration (Peeters et al ., ). Cytochrome P450 2E1 (CYP2E1) is highly expressed in rat brain mitochondria, and is also found in different cell compartments, including astrocytic end‐feet (Garcia‐Suastegui et al ., ) where S100B is abundant (Fig. ).…”

Section: Interactions Of S100b With Intracellular Target Proteinsmentioning

confidence: 99%

The Zn²⁺ and Ca²⁺‐binding S100B and S100A1 proteins: beyond the myths

2020

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The S100 genes encode a conserved group of 21 vertebrate-specific EF-hand calcium-binding proteins. Since their discovery in 1965, S100 proteins have remained enigmatic in terms of their cellular functions. In this review, we summarize the calcium-and zinc-binding properties of the dimeric S100B and S100A1 proteins and highlight data that shed new light on the extracellular and intracellular regulation and functions of S100B. We point out that S100B and S100A1 homodimers are not functionally interchangeable and that in a S100A1/S100B heterodimer, S100A1 acts as a negative regulator for the ability of S100B to bind Zn 2+ . The Ca 2+ and Zn 2+ -dependent interactions of S100B with a wide array of proteins form the basis of its activities and have led to the derivation of some initial rules for S100B recognition of protein targets. However, recent findings have strongly suggested that these rules need to be revisited. Here, we describe a new consensus S100B binding motif present in intracellular and extracellular vertebrate-specific proteins and propose a new model for stable interactions of S100B dimers with full-length target proteins. A chaperone-associated function for intracellular S100B in adaptive cellular stress responses is also discussed. This review may help guide future studies on the functions of S100 proteins in general.Biological Reviews 95 (2020) 738-758

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“…It is known that individuals with low NQO1 activity and high CYP2E1 activity would potentially be more susceptible to the toxic effects of xenobiotic than those with low CYP2E1 and high NQO1 activities [ 21 ]. GST(M1/T1) is involved in the detoxification of a wide variety of potentially toxic and carcinogenic electrophiles by conjugating them to glutathione [ 22 ] and enhancing xenobiotic solubility which facilitates its elimination [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

et al. 2018

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This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU+). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU+ patients and 67 SCA-HU− patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU+ patients (p < 0.05). Moreover, they presented higher HbF, C-reactive protein, and ferritin levels and elevated MCH and MCV values (p < 0.05). Genotype frequencies of variants GA + AA of MPO −463G>A and c1c2 + c2c2 of CYP2E1 −1293G>C/−1053C>T were higher in SCA-HU+ patients (p < 0.05). Independent associations were found between the variant A allele and lower total cholesterol, between c2 allele and low alpha-1 antitrypsin and between the null GSTT1 variant and high indirect and total bilirubin in SCA-HU+ patients. In SCA-HU− patients, independent associations were found between the variant A allele and high uric acid and between c2 allele and high urea. Our results suggest that SNPs MPO −463G>A, CYP2E1 −1293G>C/−1053C>T, and GSTT1 can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations.

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The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

Cited by 79 publications

References 144 publications

Pyrethroid exposure and neurotoxicity: a mechanistic approach

Pyrethroid exposure and neurotoxicity: a mechanistic approach

The Zn²⁺ and Ca²⁺‐binding S100B and S100A1 proteins: beyond the myths

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

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The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

Cited by 79 publications

References 144 publications

Pyrethroid exposure and neurotoxicity: a mechanistic approach

Pyrethroid exposure and neurotoxicity: a mechanistic approach

The Zn2+ and Ca2+‐binding S100B and S100A1 proteins: beyond the myths

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

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Product

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The Zn²⁺ and Ca²⁺‐binding S100B and S100A1 proteins: beyond the myths